60 research outputs found
Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma – MORSECRC
Background/aim: Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland.
Patients and methods: Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics.
Results: Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy.
Conclusion: Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients.
Keywords: Austria; Chemotherapy; Germany; Switzerland; disease characteristics; targeted therapy; treatment reality
Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma - MORSECRC.
BACKGROUND/AIM
Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland.
PATIENTS AND METHODS
Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics.
RESULTS
Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy.
CONCLUSION
Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients
Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper
Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of
cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2–1.0%. Summary: Among other risk factors associated
with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for
the metabolism of FU, is well known. This is due to variants
in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and
DPD is completely lacking in approximately 0.5% of patients.
Here we describe the clinical and genetic background and
summarize recommendations for the genetic testing and
tailoring of treatment with 5-FU derivatives. The statement
was developed as a consensus statement organized by the
German Society for Hematology and Medical Oncology in
cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be
tested for the 4 most common genetic DPYD variants before
treatment with drugs containing FU. (ii) Testing forms the
basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii)
Testing may optionally be supplemented by therapeutic
drug monitorin
Higher borides and oxygen-enriched Mg-B-O inclusions as possible pinning centers in nanostructural magnesium diboride and the influence of additives on their formation
The study of high pressure (2 GPa) synthesized MgB2-based materials allows us
to conclude that higher borides (with near MgB12 stoichiometry) and
oxygen-enriched Mg-B-O inclusions can be pinning centers in nanostructural
magnesium diboride matrix (with average grain sizes of 15-37 nm). It has been
established that additions of Ti or SiC as well as manufacturing temperature
can affect the size, amount and distribution of these inclusions in the
material structure and thus, influence critical current density. The
superconducting behavior of materials with near MgB12 stoichiometry of matrix
is discussed.Comment: 4 pages, 1 figues, presented at VORTEX VI-2009, accepted for Physica
Oesophageal cancer: Exploring controversies overview of experts' opinions of Austria, Germany, France, Netherlands and Switzerland
Background: Oesophageal carcinoma is a rare disease with often dismal prognosis. Despite multiple trials addressing specific issues, currently, many questions in management remain unanswered. This work aimed to specifically address areas in the management of oesophageal cancer where high level evidence is not available, performing trials is very demanding and for many questions high-level evidence will not be available in the forseeable future. Methods: Two experts of each national, oesophageal cancer research group from Austria, France, Germany, the Netherlands and Switzerland were asked to provide statements to controversial issues. After an initial survey, further questions were formulated and answered by all experts. The answers were then discussed and qualitatively analysed for consensus and controversy. Results: Topics such as indications for PET-CT, reasons for induction chemotherapy, radiotherapy dose, the choice of definitive chemo-radiotherapy versus surgery in squamous cell cancer, the role of radiotherapy in adenocarcinoma and selected surgical issues were identified as topics of interest and discussed. Conclusion: Areas of significant controversy exist in the management of oesophageal cancer, mostly due to high-level evidence. This is not expected to change in the upcoming years
Robert Jordan's "The Eye of the World" : a fantastic phenomenon
eingereicht von Wolfgang EistererLiteraturverzeichnis: Blatt 86-90Universität Salzburg, Diplomarbeit, 2017(VLID)495480
New entity of microsecretory adenocarcinoma of salivary glands: first case with recurrence and metastases - proof of malignancy
Microsecretory adenocarcinoma (MSA) of the salivary glands is a recently described entity. Due to lack of reported metastases, in 30 cases described until now, the designation as low-grade cancer was so far solely based on demonstration of local tumor invasion and in a single case with perineural invasion. We herein describe the first documented case with local recurrence and hematogenous metastases
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